Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Nov 1;172(5):1471–1482. doi: 10.1084/jem.172.5.1471

Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells

PMCID: PMC2188657  PMID: 2230653

Abstract

Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. G., Falck J. R., Goldstein J. L., Brown M. S. Visualization of acidic organelles in intact cells by electron microscopy. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4838–4842. doi: 10.1073/pnas.81.15.4838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson R. G., Orci L. A view of acidic intracellular compartments. J Cell Biol. 1988 Mar;106(3):539–543. doi: 10.1083/jcb.106.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blum J. S., Diaz R., Diment S., Fiani M., Mayorga L., Rodman J. S., Stahl P. D. Proteolytic processing in endosomal vesicles. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):287–292. doi: 10.1101/sqb.1989.054.01.036. [DOI] [PubMed] [Google Scholar]
  4. Chesnut R. W., Colon S. M., Grey H. M. Requirements for the processing of antigens by antigen-presenting B cells. I. Functional comparison of B cell tumors and macrophages. J Immunol. 1982 Dec;129(6):2382–2388. [PubMed] [Google Scholar]
  5. Cresswell P. Intracellular class II HLA antigens are accessible to transferrin-neuraminidase conjugates internalized by receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8188–8192. doi: 10.1073/pnas.82.23.8188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foster C. A., Yokozeki H., Rappersberger K., Koning F., Volc-Platzer B., Rieger A., Coligan J. E., Wolff K., Stingl G. Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor. J Exp Med. 1990 Apr 1;171(4):997–1013. doi: 10.1084/jem.171.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
  8. Geuze H. J., Slot J. W., Schwartz A. L. Membranes of sorting organelles display lateral heterogeneity in receptor distribution. J Cell Biol. 1987 Jun;104(6):1715–1723. doi: 10.1083/jcb.104.6.1715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Geuze H. J., Slot J. W., Strous G. J., Lodish H. F., Schwartz A. L. Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis. Cell. 1983 Jan;32(1):277–287. doi: 10.1016/0092-8674(83)90518-4. [DOI] [PubMed] [Google Scholar]
  10. Hanau D., Fabre M., Schmitt D. A., Garaud J. C., Pauly G., Tongio M. M., Mayer S., Cazenave J. P. Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis "nonclassical" major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens). Proc Natl Acad Sci U S A. 1987 May;84(9):2901–2905. doi: 10.1073/pnas.84.9.2901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanau D., Fabre M., Schmitt D. A., Stampf J. L., Garaud J. C., Bieber T., Grosshans E., Benezra C., Cazenave J. P. Human epidermal Langerhans cells internalize by receptor-mediated endocytosis T6 (CD1 "NA1/34") surface antigen. Birbeck granules are involved in the intracellular traffic of the T6 antigen. J Invest Dermatol. 1987 Aug;89(2):172–177. doi: 10.1111/1523-1747.ep12470555. [DOI] [PubMed] [Google Scholar]
  12. Harding C., Levy M. A., Stahl P. Morphological analysis of ligand uptake and processing: the role of multivesicular endosomes and CURL in receptor-ligand processing. Eur J Cell Biol. 1985 Mar;36(2):230–238. [PubMed] [Google Scholar]
  13. Hopkins C. R., Trowbridge I. S. Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells. J Cell Biol. 1983 Aug;97(2):508–521. doi: 10.1083/jcb.97.2.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koch F., Heufler C., Kämpgen E., Schneeweiss D., Böck G., Schuler G. Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation. J Exp Med. 1990 Jan 1;171(1):159–171. doi: 10.1084/jem.171.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MacPherson G. G. What don't we know about dendritic cells? Res Immunol. 1989 Nov-Dec;140(9):877–926. doi: 10.1016/0923-2494(89)90046-1. [DOI] [PubMed] [Google Scholar]
  16. McCoy K. L., Miller J., Jenkins M., Ronchese F., Germain R. N., Schwartz R. H. Diminished antigen processing by endosomal acidification mutant antigen-presenting cells. J Immunol. 1989 Jul 1;143(1):29–38. [PubMed] [Google Scholar]
  17. Mellman I., Fuchs R., Helenius A. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem. 1986;55:663–700. doi: 10.1146/annurev.bi.55.070186.003311. [DOI] [PubMed] [Google Scholar]
  18. Morel P. A., Livingstone A. M., Fathman C. G. Correlation of T cell receptor V beta gene family with MHC restriction. J Exp Med. 1987 Aug 1;166(2):583–588. doi: 10.1084/jem.166.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Puré E., Inaba K., Crowley M. T., Tardelli L., Witmer-Pack M. D., Ruberti G., Fathman G., Steinman R. M. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J Exp Med. 1990 Nov 1;172(5):1459–1469. doi: 10.1084/jem.172.5.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Romani N., Lenz A., Glassel H., Stössel H., Stanzl U., Majdic O., Fritsch P., Schuler G. Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol. 1989 Nov;93(5):600–609. doi: 10.1111/1523-1747.ep12319727. [DOI] [PubMed] [Google Scholar]
  22. Romani N., Schuler G. Structural and functional relationships between epidermal Langerhans cells and dendritic cells. Res Immunol. 1989 Nov-Dec;140(9):895–926. doi: 10.1016/0923-2494(89)90050-3. [DOI] [PubMed] [Google Scholar]
  23. Schmid S. L., Fuchs R., Male P., Mellman I. Two distinct subpopulations of endosomes involved in membrane recycling and transport to lysosomes. Cell. 1988 Jan 15;52(1):73–83. doi: 10.1016/0092-8674(88)90532-6. [DOI] [PubMed] [Google Scholar]
  24. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Steinman R., Inaba K. Immunogenicity: role of dendritic cells. Bioessays. 1989 May;10(5):145–152. doi: 10.1002/bies.950100503. [DOI] [PubMed] [Google Scholar]
  26. Streilein J. W., Grammer S. F. In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. J Immunol. 1989 Dec 15;143(12):3925–3933. [PubMed] [Google Scholar]
  27. Takigawa M., Iwatsuki K., Yamada M., Okamoto H., Imamura S. The Langerhans cell granule is an adsorptive endocytic organelle. J Invest Dermatol. 1985 Jul;85(1):12–15. doi: 10.1111/1523-1747.ep12274494. [DOI] [PubMed] [Google Scholar]
  28. Teunissen M. B., Wormmeester J., Krieg S. R., Peters P. J., Vogels I. M., Kapsenberg M. L., Bos J. D. Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. J Invest Dermatol. 1990 Feb;94(2):166–173. doi: 10.1111/1523-1747.ep12874439. [DOI] [PubMed] [Google Scholar]
  29. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  30. Willingham M. C., Pastan I. Endocytosis and exocytosis: current concepts of vesicle traffic in animal cells. Int Rev Cytol. 1984;92:51–92. doi: 10.1016/s0074-7696(08)61324-8. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES